DNA-carrier proteins for targeted gene delivery

The development of vectors for cell-specific gene delivery is a major goal of gene therapeutic strategies. Significant progress has been made in the construction of non-viral vectors that combine different functions required for gene transfer in an artificial complex. To some extent this can be achieved by complexing plasmid DNA with synthetic compounds such as lipids and polycations. Alternative approaches rely on the activities of natural or recombinant DNA-carrier proteins to achieve uptake and intracellular delivery of plasmid DNA. Nuclear proteins such as histones and members of the high mobility group protein family have been shown to condense DNA and transfect cultured cells. Some structural proteins of DNA viruses spontaneously assemble with plasmid DNA and form transfection-competent pseudocapsids. In addition, chimeric fusion proteins have been engineered that incorporate in a single polypeptide chain heterologous protein domains which facilitate binding to plasmid DNA, specific recognition of target cells, induction of receptor-mediated endocytosis, and DNA transport through intracellular compartments.